Fetal valproate syndrome occurs when a baby develops signs and symptoms as a result of an exposure to valproic acid during fetal development. Fetal exposure to valproic acid is associated with 2 to 3 times the general population risk for birth defects. This results in roughly a 6 to 9% risk of having a child with a birth defect versus the general population risk of 2 to 3%. Some children with this syndrome share common subtle facial characteristics, including thin arched eyebrows that may be spaced far apart, a wide nasal bridge, short nose with anteverted nostrils, thin upper lip, and smooth long philtrum (space between nose and lip).[1] These features may become less prominent with time.[1] Fetal valproate syndrome may also be associated with a wide range of other birth defects, as well as intellectual disability.[1][2][3][4][5] In most cases the risks for a particular symptom or defect is not currently known.

Last updated: 3/5/2010

What are the signs and symptoms of fetal valproate syndrome?

Signs and symptoms of fetal valproate syndrome can vary greatly from person to person. There are certain subtle facial features that are more commonly (but not always) associated with this syndrome.[1][2][3][4][5] These features include thin arched eyebrows that may be spaced far apart, a wide nasal bridge, short nose with anteverted nostrils, thin upper lip, and smooth long philtrum (space between nose and lip).[1] These features may become less prominent with time.[1]

Symptom and symptom severity varies from person to person. Risks for harmful effects due to prenatal exposure to valproic acid are likely influenced by a variety of factors, including drug dosage, multiple drug or drug combination, timing of drug exposure, severity of seizure disorder in the mother, predisposing genes, and folic acid intake.[2][5] In general, children of women with a seizure disorder also are at an increased risk for having a seizure disorder themselves.[5] Parental factors such as IQ and socio-economic status may also play a role in symptom and symptom severity.[5]

Signs and symptoms associated with fetal valproate exposure that have been described in medical literature are listed below by body system. Please note that some of these symptoms have been reported in only a few or a single case (these symptoms are marked with an asterisk).[2]

In addition, newborns who were exposed prenatally to seizure medications may require special care after delivery because of withdrawal symptoms. Withdrawal symptoms include feeding difficulties, low blood sugar (hypoglycemia), jitteriness, irritability, and low body temperature (hypothermia). Other symptoms may include poor muscle tone, and joint laxity.[2]

Some children with fetal valproate syndrome show delays in development, autistic features, and/or intellectual disability. In general, the most commonly affected developmental aspect is speech and language.[2] In addition some children have motor delays which may cause clumsiness and impair daily living skills, such as getting dressed, handwriting, riding a bike and swimming. Toilet-training may also be delayed, however most children do achieve this milestone.[2] Lastly, some children with fetal valproate syndrome have difficulty with social interaction, which may prompt investigation for autistic spectrum disorder.[2]

Last updated: 3/5/2010

How is fetal valproate syndrome diagnosed?

Diagnosis of fetal valproate syndrome requires a pregnancy history that includes exposure to valproic acid. Fetal valproate syndrome is a diagnosis of exclusion. This means that all other syndromes that could account for the symptoms in the infant or child are ruled out prior to making the diagnosis of fetal valproate syndrome. Fetal valproate syndrome can be difficult to diagnose, particularly when the characteristic facial features are absent.[2][3]

Last updated: 3/5/2010

How might fetal valproate syndrome be treated?

Currently there are no specific treatments for fetal valproate syndrome. Each symptom or birth defect associated with fetal valproate syndrome are managed individually, and may require a team of specialist. To read about different types of specialists and what they do, you can visit the following link to Harvard Medical School’s Family Health Guide:http://www.health.harvard.edu/fhg/specialists.shtml

In general, children with fetal valproate syndrome who show delays in comprehension and expression of speech, may be benefited by early speech therapy.[2] Physiotherapy may benefit children with motor delays.[2] Also some children with fetal valproate syndrome may require extra help in school.[2] The following resource may be helpful for families with a child with developmental, learning, or behavioral issues.